Hyperglycemic oxoaldehyde, glyoxal, causes barrier dysfunction, cytoskeletal alterations, and inhibition of angiogenesis in vascular endothelial cells

Aminoguanidine protection

Sean M. Sliman, Timothy D. Eubank, Sainath R. Kotha, M. Lakshmi Kuppusamy, Shariq I. Sherwani, Elizabeth Susan O.Connor Butler, Periannan Kuppusamy, Sashwati Roy, Clay B. Marsh, David Stern, Narasimham L. Parinandi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Vascular endothelium is vulnerable to the attack of glucose-derived oxoaldehydes (glyoxal and methylglyoxal) during diabetes, through the formation of advanced glycation end products (AGEs). Although aminoguanidine (AG) has been shown to protect against the AGE-induced adverse effects, its protection against the glyoxal-induced alterations in vascular endothelial cells (ECs) such as cytotoxicity, barrier dysfunction, and inhibition of angiogenesis has not been reported and we investigated this in the bovine pulmonary artery ECs (BPAECs). The results showed that glyoxal (1-10 mM) significantly induced cytotoxicity and mitochondrial dysfunction in a dose- and time-dependent (4-12 h) fashion in ECs. Glyoxal was also observed to significantly inhibit EC proliferation. The study also revealed that glyoxal induced EC barrier dysfunction (loss of trans-endothelial electrical resistance), actin cytoskeletal rearrangement, and tight junction alterations in BPAECs. Furthermore, the results revealed that glyoxal significantly inhibited in vitro angiogenesis on the Matrigel. For the first time, this study demonstrated that AG significantly protected against the glyoxal-induced cytotoxicity, barrier dysfunction, cytoskeletal rearrangement, and inhibition of angiogenesis in BPAECs. Therefore, AG appears as a promising protective agent in the treatment of AGE-induced vascular endothelial alterations and dysfunction during diabetes, presumably by blocking the reactivity of the sugar-derived dicarbonyls such as glyoxal and preventing the formation of AGEs.

Original languageEnglish (US)
Pages (from-to)9-26
Number of pages18
JournalMolecular and Cellular Biochemistry
Volume333
Issue number1-2
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Glyoxal
Cytoprotection
Endothelial cells
Endothelial Cells
Cytotoxicity
Pulmonary Artery
Medical problems
Pyruvaldehyde
Protective Agents
Time and motion study
Advanced Glycosylation End Products
Acoustic impedance
Time and Motion Studies
Inhibition (Psychology)
pimagedine
Tight Junctions
Vascular Endothelium
Cell proliferation
Electric Impedance
Sugars

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Hyperglycemic oxoaldehyde, glyoxal, causes barrier dysfunction, cytoskeletal alterations, and inhibition of angiogenesis in vascular endothelial cells : Aminoguanidine protection. / Sliman, Sean M.; Eubank, Timothy D.; Kotha, Sainath R.; Kuppusamy, M. Lakshmi; Sherwani, Shariq I.; Butler, Elizabeth Susan O.Connor; Kuppusamy, Periannan; Roy, Sashwati; Marsh, Clay B.; Stern, David; Parinandi, Narasimham L.

In: Molecular and Cellular Biochemistry, Vol. 333, No. 1-2, 01.01.2010, p. 9-26.

Research output: Contribution to journalArticle

Sliman, Sean M. ; Eubank, Timothy D. ; Kotha, Sainath R. ; Kuppusamy, M. Lakshmi ; Sherwani, Shariq I. ; Butler, Elizabeth Susan O.Connor ; Kuppusamy, Periannan ; Roy, Sashwati ; Marsh, Clay B. ; Stern, David ; Parinandi, Narasimham L. / Hyperglycemic oxoaldehyde, glyoxal, causes barrier dysfunction, cytoskeletal alterations, and inhibition of angiogenesis in vascular endothelial cells : Aminoguanidine protection. In: Molecular and Cellular Biochemistry. 2010 ; Vol. 333, No. 1-2. pp. 9-26.
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AU - Kotha, Sainath R.

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AU - Butler, Elizabeth Susan O.Connor

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AU - Parinandi, Narasimham L.

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